Ranibizumab Does Not Worsen Retinal Degeneration in Intermediate AMD, Study Finds

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A post hoc analysis of the PREVENT trial suggests quarterly ranibizumab did not appear to affect drusen volume, drusen area, or GA progression compared to sham.

Quarterly intravitreal ranibizumab did not appear to impact drusen volume, macular thinning, or geographic atrophy (GA) progression in eyes with intermediate age-related macular degeneration (AMD), according to new research.1

The post hoc analysis of the prospective PREVENT trial revealed no statistical differences in drusen area or volume between eyes treated with ranibizumab or sham, despite marginal increases observed over 24 months in the ranibizumab-treated eyes.

“Given the lack of differences between groups for thickness and volume reductions as well as GA growth, this means that quarterly ranibizumab injections over 24 months for eyes with intermediate AMD have not aggravated or accelerated the process of retinal degeneration in comparison to the sham eyes over the study time course,” wrote the investigative team, led by Clement K. Chan, MD, Southern California Desert Retina consultants, Unifeye Vision Partners.

Nonexudative AMD constitutes most eyes with the form of severe vision loss (≥80%), with early, intermediate, and advanced disease stages. Intermediate AMD consists of eyes with ≥1 large drusen (≥125 μm) and/or pigmentary abnormalities with medium drusen, while advanced nonexudative AMD consists of eyes with GA.2 Evidence has linked the progressive reduction in macular thickness and increased macular atrophy with AMD evolution from an earlier stage to a later stage.

Primary results from the prospective, randomized, controlled, participant-masked phase I/II comparative PREVENT trial suggested no significant differences in the rate of neovascular conversion between the ranibizumab- and sham-treated groups (approximately 13% in both arms).3 For this posthoc analysis, Chan and colleagues set out to compare changes in drusen, macular dimensions, and GA between ranibizumab-treated and sham-treated eyes to determine rates of conversion to neovascular AMD over 24 months.1

Automated algorithms were utilized to measure macular and drusen dimensions, as well as to segment and quantify individual retinal layers and measure the full thickness of the macula. On spectral-domain optical coherence tomography (SD-OCT), macular thickness variables, including central subfield thickness (CST), mean cube thickness (MCT), and cube volume, were recorded by the investigative team. Masked grading for GA areas and the presence of subretinal drusenoid deposits (SDDs) were performed using fundus autofluorescence images.

The trial used the 9-step Age-Related Eye Disease Study (AREDS) severity scale to grade study images for nonexudative or atrophic AMD features. At baseline, the median AREDS severity Scale Level was 7 for both eyes receiving intravitreal ranibizumab and eyes receiving sham injection. Baseline comparisons showed most eyes in each study group had SDDs; there were no statistical differences in mean CST, drusen area, and drusen volume at baseline between groups.

At 24 months, results showed minimal differences in drusen area and volume between the ranibizumab-treated (drusen area, P = .046; drusen volume, P = .052) and sham-treated (drusen area, P = .54; drusen volume, P = .32) groups.

On the other hand, the analysis showed significant reductions in central subfield thickness (P = .006 for ranibizumab; P = .018 for sham), mean cube thickness (P <.001 for ranibizumab; P = .001 for sham), cube volume (P <.001 for ranibizumab; P = .003 for sham) when comparing 24-month data to baseline.

Overall, however, investigators found no differences in results between the 2 study groups in any of these variables (P-values ranged from 0.28 to 0.55). In addition, no substantial changes in drusen area and drusen volume were observed for the presence (P = .66 and .556, respectively) or absence (P = .189 and .069, respectively) of SDDs.

A total of 9 eyes were identified with GA in the study. Among this population, the GA growth rates over 24 months were 1.34 ± 0.79 mm2/year for ranibizumab-treated and 1.95 ± 1.73 mm2/year for sham-treated eyes, with no significant difference between the 2 groups (difference, –0.62; 95% CI, –4.45 to 3.21; P = .61). Square root transformation also revealed no statistical difference between the two groups (P = .61), suggesting GA growth was not linked to ranibizumab.

“Therefore, our study provides no evidence of increased magnitude or rate of growth in GA due to ranibizumab injections in eyes with intermediate AMD,” investigators wrote.


  1. Chan CK, Beaulieu WT, Lujan BJ, et al. Impact of Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration on Eyes With Intermediate Age-Related Macular Degeneration. Transl Vis Sci Technol. 2023;12(9):1. doi:10.1167/tvst.12.9.1
  2. Ferris FL, Wilkinson CP, Bird A, Chakravarthy U. Clinical classification of age-related macular degeneration. Ophthalmology. 2013;120:844–851.
  3. Chan CK, Lelazary M, Abraham P, et al. Prophylactic ranibizumab to prevent neovascular agerelated macular degeneration in vulnerable fellow eyes, a randomized clinical trial. Ophthalmol Retina. 2022; 6(6):484–494.